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An integrated genomic approach identifies ARID1A as a candidate tumor-suppressor gene in breast cancer
- Source :
- Mamo, A, Cavallone, L, Tuzmen, S, Chabot, C, Ferrario, C, Hassan, S, Edgren, H, Kallioniemi, O, Aleynikova, O, Przybytkowski, E, Malcolm, K, Mousses, S, Tonin, P N & Basik, M 2012, ' An integrated genomic approach identifies ARID1A as a candidate tumor-suppressor gene in breast cancer ', Oncogene, vol. 31, no. 16, pp. 2090-2100 . https://doi.org/10.1038/onc.2011.386
- Publication Year :
- 2011
- Publisher :
- Springer Science and Business Media LLC, 2011.
-
Abstract
- Tumor-suppressor genes (TSGs) have been classically defined as genes whose loss of function in tumor cells contributes to the formation and/or maintenance of the tumor phenotype. TSGs containing nonsense mutations may not be expressed because of nonsense-mediated RNA decay (NMD). We combined inhibition of the NMD process, which clears transcripts that contain nonsense mutations, with the application of high-density single-nucleotide polymorphism arrays analysis to discriminate allelic content in order to identify candidate TSGs in five breast cancer cell lines. We identified ARID1A as a target of NMD in the T47D breast cancer cell line, likely as a consequence of a mutation in exon-9, which introduces a premature stop codon at position Q944. ARID1A encodes a human homolog of yeast SWI1, which is an integral member of the hSWI/SNF complex, an ATP-dependent, chromatin-remodeling, multiple-subunit enzyme. Although we did not find any somatic mutations in 11 breast tumors, which show DNA copy-number loss at the 1p36 locus adjacent to ARID1A, we show that low ARID1A RNA or nuclear protein expression is associated with more aggressive breast cancer phenotypes, such as high tumor grade, in two independent cohorts of over 200 human breast cancer cases each. We also found that low ARID1A nuclear expression becomes more prevalent during the later stages of breast tumor progression. Finally, we found that ARID1A re-expression in the T47D cell line results in significant inhibition of colony formation in soft agar. These results suggest that ARID1A may be a candidate TSG in breast cancer.
- Subjects :
- Cancer Research
DNA Copy Number Variations
ARID1A
Nonsense mutation
Breast Neoplasms
Biology
Transfection
medicine.disease_cause
03 medical and health sciences
0302 clinical medicine
Breast cancer
SDG 3 - Good Health and Well-being
Cell Line, Tumor
Genetics
medicine
Humans
Genes, Tumor Suppressor
Molecular Biology
Gene
030304 developmental biology
0303 health sciences
Nuclear Proteins
Cell cycle
medicine.disease
Phenotype
Candidate Tumor Suppressor Gene
DNA-Binding Proteins
Chromosomes, Human, Pair 1
Codon, Nonsense
030220 oncology & carcinogenesis
Cancer research
RNA
Female
Carcinogenesis
Transcription Factors
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 31
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....038b83a14ea0fe2f0a98fbab99bbc05e